title: Upregulated expression of FGF13/FHF2 mediates resistance to platinum drugs in cervical cancer cells.
abstract: Cancer cells often develop drug resistance. In cisplatin-resistant HeLa cisR cells, fibroblast growth factor 13 (FGF13/FHF2) gene and protein expression was strongly upregulated, and intracellular platinum concentrations were kept low. When the FGF13 expression was suppressed, both the cells' resistance to platinum drugs and their ability to keep intracellular platinum low were abolished. Overexpression of FGF13 in parent cells led to greater resistance to cisplatin and reductions in the intracellular platinum concentration. These cisplatin-resistant cells also showed increased resistance to copper. In preoperative cervical cancer biopsy samples from poor prognoses patients after cisplatin chemoradiotherapy, FGF13-positive cells were detected more abundantly than in the biopsy samples from patients with good prognoses. These results suggest that FGF13 plays a pivotal role in mediating resistance to platinum drugs, possibly via a mechanism shared by platinum and copper. Our results point to FGF13 as a novel target and useful prognostic guide for cancer therapy.
authors.affiliation: Signaling Molecules Research Group, Biomedical Research Institute, National Institute of Advanced Industrial Science and Technology (AIST), Tsukuba, Ibaraki 305-8566, Japan.
authors.forename: Tomoko
authors.initials: T
authors.lastname: Okada
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Murata
authors.forename: Ryoma
authors.initials: R
authors.lastname: Hirose
authors.forename: Chie
authors.initials: C
authors.lastname: Matsuda
authors.forename: Tsunehiko
authors.initials: T
authors.lastname: Komatsu
authors.forename: Masahiko
authors.initials: M
authors.lastname: Ikekita
authors.forename: Miyako
authors.initials: M
authors.lastname: Nakawatari
authors.forename: Fumiaki
authors.initials: F
authors.lastname: Nakayama
authors.forename: Masaru
authors.initials: M
authors.lastname: Wakatsuki
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Ohno
authors.forename: Shingo
authors.initials: S
authors.lastname: Kato
authors.forename: Takashi
authors.initials: T
authors.lastname: Imai
authors.forename: Toru
authors.initials: T
authors.lastname: Imamura
mesh_terms: D000328:Adult; D017398:Alternative Splicing; D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D045744:Cell Line, Tumor; D002945:Cisplatin / Q000494:pharmacology* / Q000627:therapeutic use; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D005260:Female; D005346:Fibroblast Growth Factors / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic; D055785:Gene Knockdown Techniques; D006367:HeLa Cells; D006801:Humans; D008875:Middle Aged; D009367:Neoplasm Staging; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D016896:Treatment Outcome; D015854:Up-Regulation; D002583:Uterine Cervical Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000401:mortality / Q000473:pathology
chemical_list: D000970:Antineoplastic Agents; D012333:RNA, Messenger; C108111:fibroblast growth factor 13; D005346:Fibroblast Growth Factors; D002945:Cisplatin